Project Summary HudsonAlpha Institute for Biotechnology The goal of this proposal is to use whole genome sequencing (WGS) to diagnose ill neonates of diverse backgrounds in the Deep South, to increase patient and provider familiarity with genomic testing, and to provide and evaluate resources to facilitate the expanded utilization of clinical genomic testing. This project will be a collaboration between genomic researchers and educators at the HudsonAlpha Institute for Biotechnology, clinicians and outcomes experts at the University of Alabama at Birmingham, clinicians at the University of Mississippi Medical Center and Druid City Hospital, and investigators at the University of Louisville interested in the ethical, legal, and social consequences of returning genetic results. 2,000 infants with signs suggestive of a genetic disorder being treated at a neonatal intensive care unit (NICU) in which African-American and rural populations are highly represented will be enrolled. WGS will be used to identify pathogenic variation in DNA from these infants. Stakeholders, including parents, clinicians, and community leaders, will be engaged to develop culturally adapted educational materials and to equip non-genetics providers to return WGS results. Parents will be provided with these materials through a web portal, the Genome Gateway, and will be placed into one of two arms of a randomized trial to compare the effectiveness technology-assisted WGS result delivery by non-genetics providers relative to result delivery from genetic counselors. A health care cost analysis will be conducted to compare children who received WGS relative to comparator children who did not. The final aim will serve to disseminate study findings and gather feedback from key stakeholders to promote uptake and broader access to clinical sequencing technologies. This study will address discrepancies in participation in genomic research by diverse racial/ethnic groups and the need for educational support to facilitate progress towards safer, more effective, and more equitably distributed genomic medicine. of